Prognostic value of interim post-treatment SPECT/CT following lutetium-177 (177Lu)-PSMA therapy in patients with metastatic castration-resistant prostate cancer: a systematic review and meta-analysis.

BACKGROUND

Lutetium-177 (177Lu)-PSMA radioligand therapy (RLT) is established for metastatic castration-resistant prostate cancer (mCRPC), but radiologic monitoring during the treatment lacks standardization. While interim PSMA PET/CT offers accuracy, post-treatment 177Lu-PSMA SPECT/CT provides practical advantages for early response assessment. This systematic review and meta-analysis evaluates the prognostic value of interim post-treatment SPECT/CT parameters on survival outcomes in mCRPC patients.

METHODS

Following PRISMA guidelines and PICO framework, PubMed/MEDLINE, Scopus, and Google Scholar were searched up to December 2025 for studies on mCRPC patients receiving 177Lu-PSMA RLT with early post-treatment SPECT/CT. Inclusion required cohort designs reporting hazard ratios (HRs) for overall survival (OS) and PSA-progression-free survival (PSA-PFS). Data extraction included study characteristics, imaging protocols, and outcomes. Quality was assessed using the Oxford CEBM tool. Random-effects meta-analysis pooled HRs; heterogeneity (I 2) and publication bias (funnel plots, Egger's test, trim-and-fill) were evaluated.

RESULTS

Seven studies (648 patients) were included. Pooled HRs showed emerging new lesions associated with worse OS (HR = 2.78, 95% CI: 1.91-4.06, p < 0.001) and PSA-PFS (HR = 4.72, 95% CI: 1.57-14.15, p = 0.006). Total tumor volume (TTV) increases predicted inferior OS (HR = 1.80, 95% CI: 1.29-2.50, p < 0.001) and PSA-PFS (HR = 2.86, 95% CI: 2.12-3.85, p < 0.001). SUVmean and SUVmax reductions were non-significant. Heterogeneity was low-moderate and publication bias had minimal impact post-adjustment.

CONCLUSION

Interim 177Lu-PSMA SPECT/CT offers prognostic insights, with new lesions and TTV increases signaling poor outcomes. Standardization and prospective validation are needed to integrate it into clinical practice.